This federal Project Grant award from the National Institute of General Medical Sciences (NIGMS), Biomedical Research and Research Training program (CFDA 93.859), provides $404,792 to Yale University to conduct research focused on understanding the mechanisms regulating telomere length, protection, and replication. The award period runs from January 21, 2025 to December 31, 2029. The research aims to yield new insights into how telomeres are maintained and replicated, with potential implications for understanding and treating human diseases like cancer and aging. Key activities include using biochemical, structural, cellular, and genetic approaches to explore a potential phospho-dephospho switch in the human POT1 protein that could coordinate telomere length maintenance. The project will also mechanistically examine how the TRF2-RAP1 complex of the shelterin complex protects telomeres from homology-directed repair, as well as how the replication factor Claspin resolves telomere replication stress. The research leverages innovative techniques like telomere D-loop assays and COMET-FISH to visualize and measure telomere replication dynamics.
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